tbuckley/cabot-search huggingface dataset:
Abstract 15152: Contributing Causes of Death in US Males With Muscular Dystrophy Across the Lifespan
Authors: Jaclyn Giafaglione, Deipanjan Nandi, Emily Hayes, Lydia Wright
Journal: Circulation (2022)

Introduction: The muscular dystrophies are a group of disorders affecting skeletal, cardiac, and respiratory muscles. Advances in care have been reported to have shifted mortality from respiratory to cardiac etiology in cohort studies. Changes in cause of mortality at the population level using Untied States national death certificate data were assessed. Methods: The CDC Wonder database was queried for male muscular dystrophy patients in the US utilizing the ICD 10 code G71.0. Cause of death and age were evaluated between 1999 and 2020 in 1 year increments. Distribution of death age was compared between those who died with heart failure and those who died with respiratory failure as contributing causes of death. Trends in median death age over time were evaluated for all groups. Results: There were a total of 12,109 deaths attributed to muscular dystrophy over the study period. Heart failure contributed to 2,419 (20%) of deaths, while respiratory failure contributed to 3,763 (31%). Deaths overall were most common in the 3 rd decade of life, while those who died with contributory heart failure died earlier compared to those with contributory respiratory failure (Figure A). The median death age has increased over time for all causes (p= &lt;0.001), though the magnitude of the change was smallest and median death age remained lowest for those with heart failure as a contributing cause (Figure B). Conclusions: While death certificate data may be incomplete and not represent the full muscular dystrophy cohort, this data supports that the median death age for patients with muscular dystrophy is increasing over time. Those with heart failure contributing to death continue to die at younger ages, suggesting opportunities for further improvement in cardiac care for these patients.
Abstract 15004: Characterization of Hypertrophic Cardiomyopathy Caused by Mutations in Four and a Half Lim Domains 1 Gene
Authors: Cason Marco, Maria-Angela losi, Felice Borrelli, Chiara Calore, Grazia Canciello, Fiore Manganelli, Stefano Tozza, Luca Bello, Suet Nee Chen, Lingaonan He, Maria Bueno Marinas, Rudy Celeghin, Martina Perazzolo Marra, Gaetano Todde, Giulia Frisso, Matthew Taylor, Kalliopi Pilichou, Raffaella Lombardi
Journal: Circulation (2022)

Background: Mutations in Four and Half Lim domain 1 ( FHL1 ), an X-chromosome gene, have been described in rare cases of Hypertrophic Cardiomyopathy (HCM), mainly associated with myopathy. The current knowledge of the outcome of HCM caused by FHL1 mutations relies only on isolated case series. Objective: We aim to establish the prevalence of FHL1 mutations in a large population with overt HCM and clinically characterize HCM patients carrying FHL1 pathogenic and likely pathogenic genetic variants. Methods: From a total population of 794 HCM patients from 3 Referral Centers for hereditary cardiomyopathies, 349 HCM probands, who tested negative for sarcomeric mutations, were genetically screened by using Next Generation Panels including FHL1 . Moreover, all patients underwent personal and family history collection, physical examination, 12-lead electrocardiogram and echocardiography; while Cardiac Magnetic Resonance (CMR) was performed in a subgroup. Clinical and genetic data of FHL1 mutation carriers from our cohort were pooled with those of 52 FHL1 positive HCM cases from literature. Results: We identified 2 FHL1 pathogenic and 2 likely pathogenic variants (1 missense: c.764G&gt;C; 2 duplications: c.762dup and c.599dupT; and 1 deletion: c.210delG) in 6 HCM probands (0.8% of all HCM and 1.7 % of non sarcomeric HCM). As shown in Fig.1 A, pooled analysis suggested that clinical phenotype of FHL1-HCM was characterized by early-onset, severe diastolic dysfunction independently from the degree of hypertrophy and fibrosis at CMR (Fig 1 B), high sudden death risk, increased incidence of atrial fibrillation and evolution toward heart failure requiring heart transplantation, and variable skeletal muscle involvement. Conclusions: HCM patients carrying FHL1 mutations present with a worse prognosis as compared with the classic sarcomeric-HCM. A better characterization of these patients is needed for a personalized preventive and therapeutic approach.
Abstract 15922: Effect of Glp-1 Receptor Agonists on Systolic Blood Pressure in Patients With Overweight or Obesity: A Network Meta-Analysis
Authors: Muhammad Shariq S Usman, Tariq J Siddiqi, Asad Ali Siddiqui, Abraish Ali, Izza Shahid
Journal: Circulation (2022)

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to reduce weight in patients with overweight or obesity. However, their effect on systolic blood pressure (SBP) remains less well-established. We conducted a network meta-analysis to evaluate the effect of different drug-dose combinations of GLP-1 RAs on SBP in this population. Methods: Electronic databases were searched through January 2022 for RCTs which evaluated the efficacy of different doses of semaglutide, liraglutide, efpeglenatide, and exenatide in obese patients with and without T2DM. Systolic blood pressure (SBP) was chosen as the primary endpoint. A frequentist network meta-analysis using random-effects model was conducted, and pooled estimates were reported as mean differences (MD) with 95% confidence intervals (CI). Results: A total of 20 RCTs were included in the analysis. Among individuals with T2DM, liraglutide &lt;2 mg once daily (QD) showed the greatest reduction in SBP (MD: -3.78 [-5.63; -1.15]), followed by exenatide 10 ug twice daily (BID) (MD: -3.39 [-5.63; -1.15]), and semaglutide ≥1mg once weekly (QW) (MD: -3.28 [–5.68; –0.88]), when compared with placebo. Among individuals without diabetes, efpeglenatide ≤ 6 mg QW showed the greatest reduction in SBP (MD: -6.00 [-9.89; -2.11]), followed by semaglutide ≥ 1 mg QW (MD: -4.54 [–5.69; –3.39]), and semaglutide &lt;1mg QW (MD: -4.51 [–5.49; –3.54]). The figure shows how each drug/dose combination compares with others. Conclusions: This network meta-analysis suggests liraglutide &lt;2mg QD is the most efficacious GLP-1 RA in lowering SBP in obese patients with T2DM. For obese patients without diabetes, efpeglenatide ≤6mg QW is the most effective.
Abstract 15094: Inflammatory Genotype-Phenotype Interaction Moderates Response to a Cardiovascular Disease Risk Reduction Intervention in Rural Adults at-Risk for Cardiovascular Disease
Authors: Kaitlin V Key, Debra K Moser, Lorri A Morford, Terry Lennie, Mary Kay Rayens, Martha J Biddle, Gia Mudd Martin
Journal: Circulation (2022)

Introduction: Systemic inflammation and inflammatory genotypes have been associated with cardiovascular disease (CVD) risk, with associations between C-reactive protein (CRP), a marker of systemic inflammation, the rs1205 polymorphism on the CRP gene, and CVD risk among the most well-studied. However, little is known about the effect of systemic inflammation and associated genotypes on response to CVD risk reducing interventions. The purpose of this study was to examine whether high sensitivity C-reactive protein (hsCRP) moderated the association between rs1205 genotype and response to a CVD lifestyle-focused risk-reduction intervention. Methods: Participants were 400 rural adults with 2+ CVD risk factors participating in the HeartHealth in Rural Kentucky study. At baseline, we measured serum hsCRP and genotyped participants for the rs1205 polymorphism. Genotypes were categorized as CC or CT/TT. Response to the HeartHealth intervention was estimated by the pre-to-post intervention percent change in Framingham Risk Score (FRS). A moderation analysis with subsequent floodlight analysis was conducted using PROCESS macro for SPSS. Analyses were adjusted for body mass index, education, financial status, marital status, and insurance status. Results: Participants were aged 51.2±13.3 years and predominantly female (73.6%). The rs1205 genotype’s effect on FRS change was moderated by hsCRP (p=.004). Subsequent floodlight analysis revealed that rs1205 genotype had a larger effect on FRS change among those with lower (&lt;0.54 mg/L; p=.05) and higher (&gt;7.67 mg/L; p=.05) hsCRP as compared to those with hsCRP ranging from 0.54-7.67 mg/L (p &gt;.05). Among those with lower hsCRP, those with the CC genotype had a larger decrease in FRS than those with CT/TT genotypes. Among those with high hsCRP, those with the CT/TT genotypes experienced a larger decrease in FRS to those with the CC genotype. Conclusion: Findings suggest that inflammatory phenotype moderates the relationship between inflammatory genotype and response to a CVD risk reduction intervention. This highlights the need to examine additional inflammatory markers and inflammatory genotypes to determine the impact of inflammation and genetics on responsiveness to CVD risk reduction interventions.
Abstract 15438: Long-Term Outcomes of Bariatric Surgery in Patients With Atrial Fibrillation
Authors: Samarthkumar J Thakkar, Harsh P Patel, Bhavin Patel, Bryan E-Xin Tan, Harigopal Sandhyavenu, Sahith Reddy Thotamgari, Aakash Sheth, Hemanth Krishna Boppana, Krutarth K Pandya, Kunal N Patel, Devesh Rai, Nadeen N Faza, Mohan Rao, Christopher V Desimone, Abhishek Deshmukh
Journal: Circulation (2022)

Introduction: Obesity is associated with a higher burden of atrial fibrillation (AF) and related complications. Hypothesis: Bariatric surgery in patients with AF is associated with a reduction in mortality and long-term complications at 1 year. Methods: Patients with AF who underwent bariatric surgery were identified by analyzing the nationwide readmission database and incorporating the validated ICD-10 CM codes from October 2015 to December 2019. We performed the propensity score matching to adjust the confounders and cox proportional hazard regression to generate hazard ratios. Moreover, we generated Kaplan Meier curves for time-to-event analysis. The primary endpoint was all-cause mortality at 1 year, whereas secondary endpoints were ischemic stroke, major bleeding, and AF readmission at 1 year. Results: Out of 892488 obese patients with AF, 18766 underwent bariatric surgery. After propensity score matching, 18764 patients were identified in each group. At 1-year, patients undergoing bariatric surgery had a significant reduction in mortality (2.18% vs. 2.73%, HR: 0.91, 95% CI: 0.85-0.96, p=0.001). Additionally, risk of ischemic stroke was also reduced (1.98% vs. 2.29%, HR: 0.91, 95% CI: 0.86-0.97, p=0.01), whereas no difference was noted in AF readmissions (4.02% vs. 3.34%, HR: 0.97, 95% CI: 0.92-1.04, p=0.49) and risk of major bleeding was increased (5.74% vs. 3.42%, HR: 1.17, 95% CI: 1.10-1.25, p&lt;0.0001) at 1 year in AF patients with bariatric surgery. (Figure 1) Conclusions: Bariatric surgery in patients with AF was associated with a reduction in 1-year mortality and ischemic stroke. However, the risk of major bleeding was noted to be increased and no difference was noted in AF readmission at 1 year.
Abstract 183: Prioritizing Interventions To Reduce The Caregiver Burden Among Racially And Ethnically Diverse Co-survivors Of Cardiac Arrest Survivors: A Cross-sectional National Survey Study
Authors: Jennifer F Chap, Mary M Newman, Sabine L Abukhadra, Danielle Rojas, Christine L Deforge, Isabella Tincher, Jasmine Wylie, MARTHA E LOPEZ-ANDERSON, Cindy Marchionda, Sachin Agarwal
Journal: Circulation (2022)

Introduction: Cardiac arrest (CA) co-survivors i.e., close family members of CA survivors, have high levels of caregiver burden and poor quality of life. We aim to prioritize potential patient-, and co-survivor-centric interventions that may alleviate caregiver burden. Methods: We distributed an online survey to adult, co-survivor members of the Sudden Cardiac Arrest Foundation and Parent Heart Watch national databases and CA-specific Facebook groups. Participants provided demographics, details on their loved ones’ CA, and their caregiving role. They then ranked their top choice among 8 unique interventions focusing on either patient-centric education-based needs (n=4) or co-survivor-centric resources for self-care and enhanced psychological support (n=4). The survey was developed by a multidisciplinary research team and patient and co-survivor stakeholders. Results: Of 657 responses received, 550 co-survivors (57% were between the age of 18-40 years, 65% were women, 51% of minority race/ethnicity, 53% partners or spouse, an average of 8 hours of caregiving, for an average of 5 months) with the complete ranking data, were analyzed. A total of 347 (63%) co-survivors ranked patient-centric education-based interventions as their top choice ( Figure 1 shows distributions ). A multivariate model estimating the drivers of preferences for education-based interventions over co-survivors resource-based interventions showed age&gt;40 years, direct discharge to home after CA vs inpatient rehabilitation, co-survivor witnessing the CA, or assuming the caregiver role during hospitalization or within 1-month of CA, were significant predisposing factors. Conclusions: Education-based interventions, particularly information related to their loved ones’ recovery, are the top priorities for co-survivors during the early phase of CA survivorship. Future studies should focus on developing and testing these interventions for alleviation of caregiver burden.
Abstract 14957: Validation of Echocardiography Color Doppler Velocity Reconstruction Against 4d Flow Mri in Assessment of Right Ventricular Intracardiac Flow
Authors: Brett Meyers, Jonathan Nyce, Jiacheng Zhang, Yue-Hin Loke, Pavlos Vlachos
Journal: Circulation (2022)

Introduction: Intracardiac flow imaging of the right ventricle [RV] may improve the management of congenital heart disease like repaired Tetralogy of Fallot [rTOF] or atrial shunts that cause RV dilation [RVD]. However, this is mostly performed via 4D flow magnetic resonance imaging [MRI], which has limited availability and is resource intensive. We propose the use of conventional echocardiography as a viable alternative to assess RV intracardiac flow. Hypothesis: We hypothesize that a velocity reconstruction algorithm implemented for conventional color Doppler echocardiography can resolve flow quantities with good agreement to 4D flow MRI. Methods: We retrospectively collected echos for children with rTOF/RVD and age-matched controls. Color Doppler echos of the RV were evaluated using an in-house algorithm called Doppler Velocity Reconstruction [DoVeR]. Measurements from 4D flow MRI and DoVeR were post-processed to collect hemodynamics parameters for relative pressure difference , vortex strength , total kinetic energy , and viscous energy loss . Agreement between modalities was performed by cross-correlation and L2-norm difference between indexed chamber-average timeseries measurements. Results: 10 rTOF subjects, 3 RVD, and 7 age-matched controls were identified. There was qualitative agreement in spatial and time series measurements between DoVeR and 4D flow MRI (Figure 1). For timeseries measurements, there was strong correlation (median R &gt; 0.85) with low differences (median L2 &lt; 15%) between DoVer and 4D flow MRI. Conclusions: A color Doppler reconstruction method, DoVeR, can effectively measure hemodyanmics parameters using conventional color Doppler echocardiography, with strong agreement against 4D flow MRI. Figure 1: Left – Flow field overlaid onto pressure reconstruction and pressure difference estimates between DoVeR and 4D flow modalities. Right – Correlation coefficient and difference between modality timeseries measurements.
Abstract 14979: MicroRNA-342-3p Regulates Post-Ischemic Angiogenesis in Diabetic Mice
Authors: Anurag Jamaiyar, Jingshu Chen, Carmel Assa, Henry Cheng, Daniel Perez-Cremades, Mark W Feinberg
Journal: Circulation (2022)

Introduction: Diabetic patients are more likely to suffer from adverse cardiovascular events such as myocardial infarction (MI) compared to non-diabetics. Angiogenesis is crucial to limiting infarct size. However, this angiogenic response is blunted in patients with diabetes. MicroRNAs (miRNAs) have been shown to affect both physiological and pathological angiogenesis. However, the role of miRNAs in MI-associated angiogenesis in diabetes remains poorly defined. Here, we describe a novel role of miRNA-342-3p in angiogenesis following ischemic injury to the myocardium. Methods: We performed RNA sequencing on cardiac endothelial cells of Ldlr-deficient mice on either chow or high fat sucrose containing (HFSC) diet at 0-, 3-, 7- and 14-days post-MI. Gain and loss of function studies, functional assays, RNA-seq, bioinformatics, RNA-FISH, and light-sheet microscopy were used to ascertain the function and mechanism of this miRNA. Results: miR-342-3p was upregulated in cardiac ECs during the vascular remodeling phase post-MI in chow-fed mice compared to the HFSC-fed group. Overexpression of miR-342-3p promotes the number of endothelial sprouts (140% vs control), cumulative sprout length (311% vs control) and scratch closure (AUC 83% vs control, p &lt;0.0001) in endothelial cells (ECs), whereas its inhibition had anti-angiogenic effects. Capillary density and EC proliferation (ki67 + /CD31 + ) increased by 107% and154% respectively in the border zone of hearts injected with miR-342-3p mimics compared to control in HFSC diet fed Ldlr -/- mice 7 days after permanent LAD ligation. Using a combination of RNA-seq and prediction algorithms, Decorin (DCN), a small Leucine rich protein with anti-angiogenic properties, was identified as a target of miR-342-3p. Western blot analysis confirmed significant knockdown of Decorin protein by 94% in HUVECs transfected with miR-342-3p mimics compared to controls. RNA seq profiling of overexpressing ECs implicated the ID1 signaling pathway. Conclusion: These results identify a novel role for miR-342-3p in the regulation of angiogenesis post-MI in diabetes. miR-342-3p overexpression rescues impaired angiogenesis in diabetic hearts via the suppression of Decorin, providing new targets for therapeutic angiogenesis.
Abstract 15472: Skeletal Muscle Sirt3 Deficiency Remotely Regulates Pulmonary Vascular Remodeling Via Loxl2-cnpy2-p53 Axis In Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
Authors: Jia-Rong Jheng, Kentaro Noda, Yang Bai, Huot Joshua, Gunner Halliday, Todd Cook, Marc A Simon, Daniel E Forman, Andrea Bonetto, Roberto F Machado, Mark T Gladwin, Yen C Lai
Journal: Circulation (2022)

Background: Pulmonary hypertension in the context of heart failure with preserved ejection fraction (PH-HFpEF) is the most common cause of PH worldwide. However, major pathways involved in the regulation of PH-HFpEF are still not well understood. We have previously reported a role of skeletal muscle sirtuin-3 (SIRT3) in PH-HFpEF. In the present study, we aimed to investigate how skeletal muscle SIRT3 defects remotely affect pulmonary vascular health in PH-HFpEF. Methods and Results: Using global mass spectrometry-based comparative analysis, we found increased secretion of lysyl oxidase homolog 2 (LOXL2) in SIRT3-deficeint skeletal muscle. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3 skm-/- mice, rats with experimental PH-HFpEF (SU5416/Obese ZSF1, Ob-Su), and patients with PH-HFpEF. Additionally, expression levels of canopy fibroblast growth factor signaling regulator&amp;nbsp;2 (CNPY2), a known angiogenic and proliferative factor, were increased in PASMCs obtained from Sirt3 skm-/- mice and Ob-Su rats, suggesting a potential role of CNPY2 as a molecular target of skeletal muscle SIRT3-LOXL2 signaling in PASMCs. Treatment with LOXL2 recombinant protein resulted in increased levels of CNPY2, PCNA, and cellular proliferation in vitro in PASMCs. LOXL2 treatment, as well as CNPY2 overexpression, decreased the levels of tumor suppressor p53 in PASMCs. In addition, CNPY2 overexpression also decreased CNPY2 expression level in PASMCs. Media conditioned by SIRT3-deficient skeletal muscle cells increased CNPY2 expression in PASMCs, concomitant with decreased p53 and enhanced PCNA. Finally, knockdown of both SIRT3 and LOXL2 in skeletal muscle cells and/or suppression of LOXL2 with β-aminopropionitrile&amp;nbsp;(BAPN) restored CNPY2, p53, and PCNA levels in PASMCs. Conclusions: These studies reveal a new endocrine signaling axis that links skeletal muscle SIRT3 deficiency to remote CNPY2 -p53 regulation in the pulmonary vasculature through myokine LOXL2. Our data may also identify skeletal muscle SIRT3, myokine LOXL2, CNPY2, and p53 as potential targets for the treatment of PH-HFpEF.
Abstract 15799: Autograft External Support is Associated With Fewer Aortic Reinterventions in Patients &gt;13 Years Old After the Ross Procedure
Authors: Carlos Diaz-Castrillon, MELITA VIEGAS, Shwetabh Tarun, Jordann Lewis, Tamara Maihle, Mario Castro, Victor O Morell
Journal: Circulation (2022)

Objective: To assess intermediate outcomes among patients older than 13 years old who underwent a Ross procedure at a single center and to describe the relationship of external reinforcement with the need for aortic reinterventions Methods: Retrospective analysis of a single center clinical records from 2005 to 2020. Comparative analysis of baseline and perioperative variables was done using non-parametric test between Ross procedure and modified Ross procedure. Kaplan Meier function was used to evaluate the survival free from aortic reintervention. Results: A total of 40 patients with a median age of 17.9 years (IQR 15.4 - 20.1), 88% (n= 35) males and median weight of 64.1 Kg (IQR 55.8-83.2) were included, where 15% (n= 6) had a Ross-Konno procedure and 85% (n= 34) a Ross procedure. Overall, 70% (n= 28) of the patients had the pulmonary autograft reinforced with a woven vascular graft, with a median size of 28 mm (IQR 26 - 28). The most common indication for surgery was a mixed stenotic/insufficiency lesion in 75% (n=10) of cases, and the most common anatomic configuration was a bicuspid valve in 73% (n= 29); 65% (n= 26) of the patients had had a pre-Ross aortic intervention. No differences were observed between the reinforced and non-reinforce group in terms of age (16 vs 18 years: p=0.29), and weight (63 vs. 69 kg; p=0.57) nor indication for surgery (Table 1). After a median follow up time of 5.1 years (IQR 2.6 - 7.8), 25% (n=3) of the non-reinforced Ross had required aortic reinterventions compared to 4% (n=1) with the reinforced group. The survival free from aortic reintervention at 5 years was 96% (CI 87 - 99) in the cohort, without differences in the Kaplan Meier curves between the 2 groups (log rank= 0.18) Conclusion: Intermediate outcomes after the Ross procedure in patients &gt;13 years old are favorable, with a lower rate of reintervention in patients with a reinforced autograft. Long term outcomes are needed to further elucidate the greater impact of external support of valve competency.